ISSN:1660-8151    

DOI:10.1159/000189131

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Recent studies using experimental models of glomerular disease have not only elucidated the pathophysiologic basis of glomerular disease, but have also identified potential new treatments. In this review, we will provide examples of how cytokines and cytokine antagonists may be used in the future treatment of glomerular disease. Treatments will be presented for each of the pathophysiologic phases of disease, beginning with the etiology, the development of a nephritogenic immune response, the mechanisms by which glomerular injury occurs, the response of the glomerulus to injury that results in cell proliferation and matrix expansion, and the factors that lead to healing or scarring. Special emphasis is placed on the cytokines interleukin 1 beta and tumor necrosis factor alpha, which are proinflammatory cytokines that potentiate neutrophil-and monocyte-mediated glomerular injury, and on the growth factors platelet-derived growth factor and transforming growth factor beta, which are involved in cell proliferation and matrix expansion that occur as glomerular cells respond to injury. The identification of the specific mediators involved in glomerular disease should provide new therapies that are more specific and less toxic than current conventional immunosuppressive regimens.

ISSN:1660-8151    

DOI:10.1159/000189132

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The rationale behind a proposed use of heparins for the control of proliferative nephritides is presented. Heparins stop adhesion of leucocytes to endothelial cells, they are anti-complementary, they modulate the activities of phagocytes and they stop the proliferation of mesangial cells or vascular smooth muscle cells. Heparins prevent the release of endothelin-1 and potentiate the action of constitutive nitric oxide. Low-molecular-weight heparins or pentosan polysulphate are now favoured.

ISSN:1660-8151    

DOI:10.1159/000189133

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Diabetic patients (n = 23) with chronic renal failure (CRF) accumulate the creatinine (Cr) oxidative metabolites creatol (CTL) and methylguanidine (MG; a uremic toxin) in their sera. Analysis of serum CTL, a key intermediate in mammalian Cr catabolism into MG, is shown to offer some useful diagnostic information on CRF, especially in the determination of an initial stage of pathological renal failure. The sera of all diabetic (n = 23) and nondiabetic (n = 20) patients with CRF (s-Cr > 1.25 mg/dl) contained s-CTL ( > 2 μg/dl), whereas those from normal subjects (n = 18) and diabetic patients (n = 18) without CRF contained no detectable s-CTL. A similar accumulation of s-MG was observed, but only when s-Cr was higher than 2.0 mg/dl. Although each s-CTL (Y: μg/dl, Y’: mol/l) and s-MG level (Z: μg/dl, Z’: mol/l) is highly correlated with s-Cr (X: mg/dl, X’: mol/l) in a normal equation, Y or Z = AX + B, an alternative correlation in a second-order equation, Y or Z = αX2 + βX, could also fit well. Since the quadratic equation can be convertible to Y/X or Z/X = αX + β [Y’/X’ or Z’/X’ = α’X + β’] and active oxygen species, especially hydroxyl radicals, convert Cr into CTL, Y’X, Y’/X’, Z/X and Z’/X’ values which might be a kind of indices for oxygen stress (oxidative stress) increased in proportion to the increased severity of CRF in such patients. Although its meaning and interpretation are still debatable, diabetic CRF patients had a significantly higher α’ value (2.2) than that (0.89) of nondiabetic CRF patients. All serum values for

ISSN:1660-8151    

DOI:10.1159/000189134

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Macrophages seem to play an important role in the development of glomerulosclerosis. In the present study we evaluated the effect of morphine, an active metabolite of heroin, on the migration of monocytes across a filter in a modified Boyden chamber. Morphine-mesangial cell interaction enhanced (p < 0.004) the migration of monocytes across the filter (control 14.2 ± 0.6 vs. morphine 22.1 ± 1.7 monocytes/HPF). Dimethylthiourea (DMTU), a free radical scavenger, attenuated this effect of morphine. Morphine-monocyte secretory products (MMSP) did not modulate the migration of monocytes. However, the products of interaction between mesangial cells and MMSP enhanced (p < 0.001) the passage of monocytes across the filter. Mesangial cells treated with MMSP showed mRNA expression for monocyte chemoattractant peptide-1 (MCP-1). Superoxide also induced mRNA expression for MCP-1 on MC. DMTU attenuated this effect of superoxide. Since morphine activates MC to produce superoxide and DMTU attenuated the effect of superoxide on MC, the effect of morphine on the migration of macrophages may be mediated through superoxide-induced generation of MCP-1. We conclude that morphine enhances the migration of monocytes. This effect of morphine may be contributing to the development of glomerulosclerosis in patients with heroin addictio

ISSN:1660-8151    

DOI:10.1159/000189135

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

A periodicity has been observed in thrombotic events that occur in a variety of vascular beds. There also has been a recent suggestion that there is an increased failure of hemodialysis vascular accesses due to thrombosis during the summer months. We reviewed the last 949 episodes of vascular access thrombosis and found no seasonal pattern, but a weekly pattern was noted that corresponded to the patients’ dialysis schedule. That pattern was apparently due to our technique of observation and not due to any intrinsic periodicity in the thrombosis itself. We find no evidence to support the belief in any intrinsic periodicity in hemodialysis vascular access thrombosis and since the thrombotic event itself is usually asymptomatic, any accurate assessment of a diurnal or circumseptan pattern is not possible under ordinary clinical condition

ISSN:1660-8151    

DOI:10.1159/000189136

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The role of infiltrating macrophages in the pathogenesis of acute rejection was investigated in biopsy specimens obtained from human transplanted kidneys using immunohistochemical methods. Thirty-one allograft tissue specimens obtained from 26 patients were histologically classified into 18 with acute rejection, 7 with borderline change and 6 with chronic rejection according to the Banff working classification (1993). These specimens were analyzed by avidin-biotin peroxidase complex method on frozen sections in order to examine the utility of some antimonocyte/macrophage monoclonal antibodies in differentiating acute rejection from other conditions. The ratio of CD68, CD11b, LeuM3, OKM5 and HAM56-positive infiltrating monocytes/macrophages to leukocyte common antigen (LCA)-positive cells in the renal cortex were calculated. As a result, the ratio of the positive cells for CD68, which stains mature macrophages, significantly increased in the cases of acute rejection compared with those of other groups. In addition, a strong expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed in the acute rejection group. In our study, the expression of class II major histocompatibility antigens (HLA-DR) in the proximal epithelial tubules was also strongly observed in the cases of acute rejection. It was thus concluded that the increase of CD68-positive infiltrating cells and the expression of GM-CSF may play a possible role as a reaction effector in the process of acute renal allograft rejection.

ISSN:1660-8151    

DOI:10.1159/000189137

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Vascular disease is frequent in uremics and may contribute to tissue malnutrition and damage. The aim of this study was to detect whether uremic patients show also changes of microcirculation and to evaluate the effects induced by hemodialysis (HD) session. Eleven uremics on HD (7 males, 4 females, aged 25-65 years) were studied; 11 healthy subjects, age- and sex-matched, served as controls. Skin microcirculatory basal flow (BF), maximal postischemic flow (PIF-max) and flow motion index (FMI) were determined at the upper limb contralateral to arteriovenous fistula, by means of a laser Doppler flowmeter. The measurements were taken before, at 1 and 2 h after starting HD and 30 min after the end of HD. In uremics, FMI was lower than in controls (mean ± SD: 15.2 ± 13.6 vs. 29.1 ± 7.4%; p < 0.005); just 1 h after the start of HD, a significant improvement (28.4 ± 17.7%; p < 0.01) versus basal values was observed and it persisted throughout the HD session. No statistical correlation was observed between the changes of FMI and those of plasma levels of Na+, K+, HCO3-, urea, iPTH or rate of ultrafiltration. BF and PIF-max were similar in uremics and controls, and no changes were observed during HD. Our study shows that the physiological flow motion is reduced in the skin microcirculation of uremics on HD. This abnormality is rapidly corrected by

ISSN:1660-8151    

DOI:10.1159/000189138

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of contrast media on renal function and the cortical retention of contrast media after abdominal angiography were investigated. Sixteen non-diabetic patients with predialytic chronic renal failure received either the nonionic dimeric contrast medium iodixanol or the monomeric contrast medium iohexol in a double-blind randomized study. All patients were well hydrated before, during and after angiography. Mean 99mTc-DTPA clearance was 14.0 ml/min/1.73 m2 in the iodixanol group, and 9.3 ml/min/1.73 m2 in the iohexol group at baseline. No statistically significant changes were seen after angiography. Serum creatinine increased significantly 48 and 72 h after angiography in both groups, and then normalized. Creatinine clearance was reduced only in the iohexol group, at 72-96 h. The urinary excretion of renal enzymes and of total protein did not change significantly. No patients developed oliguria or required dialysis during the 7-day observation period. Increased attenuation in the renal cortex, measured by computed tomography and probably reflecting intracellular retention of contrast medium, peaked at 24 h, and was observed in both groups during the follow-up period. Thus, although transient and minor changes in glomerular filtration rate were noted, both iodixanol and iohexol were safe for use in angiography in nondiabetic patients with severe chronic failure when the patients were well hydrated.

ISSN:1660-8151    

DOI:10.1159/000189139

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Bone mineral density was studied in 50 adult patients with renal lithiasis and metabolic diagnosis of idiopathic hypercalciuria. Thirty were premenopausal women and 20 were men under 55 years of age. Bone density at the lumbar spine (LSBD) was 0.940 ± 0.106 g/cm2 in the hypercalciuric patients compared to 1.112 ± 0.037 g/cm2 in a cohort of age- and sex-matched controls (p < 0.001). LSBD was independent of age and was negatively correlated with the duration of stone disease (r = -0.52, p < 0.001). Thus we conclude that patients with idiopathic hypercalciuria have a decrease in their LSBD that is probably related to a negative calcium balance sustained over tim

ISSN:1660-8151    

DOI:10.1159/000189140

出版商:S. Karger AG    

年代:1996

数据来源: Karger